Emerging Roles of Lipids in the Flavivirus Life Cycle

Flaviviruses such as Dengue, Zika, and West Nile virus cause a significant global health burden and have earned attention as high pandemic risk pathogens. Flaviviruses interact closely with cell membranes at every stage of their life cycle, and mounting evidence demonstrates that flaviviruses rely on specific lipids and lipid-remodeling proteins, presenting potential therapeutic opportunities for targeting the host’s lipid metabolism. Our understanding of lipid function in infection has expanded considerably in recent years, partly thanks to advances in lipidomics, cryo-electron tomography, lipid-based chemical tools, and biophysical characterization techniques. In this review, we highlight recent breakthroughs that have clarified flavivirus lipid requirements and functions, as well as ongoing technological advances in the virus-lipid interaction field poised to enable the next wave of discoveries.